Hyaluronic Acid for Medical Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: 31 March 2024 | Viewed by 8394

Special Issue Editors

UB-CARE S.r.l. Spin-Off, University of Pavia, 27100 Pavia, Italy
Interests: cell culture; microbiology; hyaluronic acid; reconstructed epidermis; molecular biology; laser treatment
Department of Dermatology and Allergology, Städtisches Klinikum Dresden, Academic Teaching Hospital, Dresden, Germany
Interests: dermatology; melanoma; psoriasis; wound healing

Special Issue Information

Dear Colleagues,

Hyaluronic acid (HA) is a glycosaminoglycan (GAG) that is structurally homogeneous between different species; therefore, it is considered a bio-renewable resource for multiple biomedical applications. Its peculiar physical and mechanical properties as well as its high biocompatibility and key role in different biological processes such as cell signaling and wound repair make it an ideal viscoelastic material for ophthalmic and orthopedic surgery, soft tissue augmentation, facial rejuvenation, and drug delivery. Recently, the high potential linked to this biopolymer has been widely recognized and has increased interest for its physico-chemical but also biological characterization through in vivo, but above all, in vitro innovative methods. Thus, this Special Issue encourages authors to submit research papers and comprehensive reviews on the most recent scientific discoveries regarding the formulation and cross-linking process with chemical agents and more as well as on the physico-chemical and biological characterization of HA-based biomaterials, always with the ultimate aim of proving their applicability in biomedical field. In this Special Issue, original research articles and reviews are welcome.

This Special Issue aims to collect the most recent scientific discoveries on the formulation and cross-linking process with chemical agents and on the physico-chemical and biological characterization of HA-based biomaterials to  improve their applicability in the biomedical field.

We look forward to receiving your contributions.

Dr. Sabrina Sommatis
Prof. Dr. Uwe Wollina
Guest Editors

Manuscript Submission Information

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Keywords

  • hydrogel synthesis
  • hydrogel structure
  • biofabrication
  • tissue engineering
  • drug delivery
  • cell encapsulation
  • wound healing

Published Papers (7 papers)

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Research

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10 pages, 1758 KiB  
Article
Strengthening the Key Features of Volumizing Fillers: Projection Capacity and Long-Term Persistence
by Killian Flégeau, Jing Jing, Camille Vantou, Romain Brusini, François Bourdon and Jimmy Faivre
Pharmaceutics 2023, 15(11), 2585; https://doi.org/10.3390/pharmaceutics15112585 - 04 Nov 2023
Viewed by 829
Abstract
Volumizing fillers aim to create or restore facial volume in fat layers. To provide strong tissue lifting and long-term persistence, gels are generally designed with stiff properties, characterized by a high storage modulus (G′). However, clinical evidence shows a discrepancy between high G′ [...] Read more.
Volumizing fillers aim to create or restore facial volume in fat layers. To provide strong tissue lifting and long-term persistence, gels are generally designed with stiff properties, characterized by a high storage modulus (G′). However, clinical evidence shows a discrepancy between high G′ and good lifting capacities, especially after skin tension has been exerted on the gel. To better explore the in vivo behavior of a gel, we first evaluated the elastic moduli of five commercial volumizers (RHA4, JUVVOL, RESVOL, RESLYFT, and BELVOL) in dynamic compression mode, E′. We further developed a Projection Index score based on the rheological assessment of creep in compression to mimic skin tension-induced stress relaxation (flattening). Finally, the ability of a gel to resist enzymatic degradation was analyzed with a multidose approach. Despite similar clinical indications, volumizers exhibited distinct behaviors. RHA4 and BELVOL showed the highest E′ values (resistance to strain), RHA4, JUVVOL, and RESVOL exhibited the greatest projection capacities, while JUVVOL and RHA4 offered the largest persistence to enzymatic degradation. In this article, we introduce the use of the Projection Index to efficiently assess the ability of a gel to lift tissues, thus increasing preclinical models’ efficiency and reducing the need for animal studies. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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12 pages, 10447 KiB  
Article
Enhancing Dental Applications: A Novel Approach for Incorporating Bioactive Substances into Textile Threads
by Marek Pokorný, Jolana Kubíčková, Jan Klemeš, Tomáš Medek, Adam Brýdl, Martina Pachovská, Tereza Hanová, Josef Chmelař and Vladimír Velebný
Pharmaceutics 2023, 15(10), 2487; https://doi.org/10.3390/pharmaceutics15102487 - 18 Oct 2023
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Abstract
In the realm of surgical and dental applications, hyaluronic acid (HA) braided threads show significant therapeutic potential due to their incorporation of pharmaceutical active ingredients. This study primarily focuses on resolving the crucial challenge of devising a deposition method that can ensure both [...] Read more.
In the realm of surgical and dental applications, hyaluronic acid (HA) braided threads show significant therapeutic potential due to their incorporation of pharmaceutical active ingredients. This study primarily focuses on resolving the crucial challenge of devising a deposition method that can ensure both precision and uniformity in the content of the active ingredient Octenidine dihydrochloride (OCT) within each segment of the threads. Our objective in this study was to develop a continuous deposition method for OCT onto a braided thread composed of 24 hyaluronic acid-based fibers, aiming for a specific OCT content of 0.125 µg/mm, while maintaining a maximum allowable deviation of ±15% in OCT content. The motivation behind designing this novel method stemmed from the necessity of employing a volatile solvent for the active agent. Conventional wetting methods proved unsuitable due to fluctuations in the solution’s concentration during deposition, and alternative methods known to us demanded intricate technical implementations. The newly introduced method offers distinct advantages, including its online processing speed, scalability potential, and cost-efficiency of the active agent solution. Additionally, it minimizes the impact on the natural polymer thread, preserving energy by obviating the need for complete thread saturation. Our research and precise apparatus development resulted in achieving the desired thread properties, with an OCT content of (1.51 ± 0.09) µg per 12 mm thread piece. These findings not only validate the suitability of this innovative method for depositing active agents but also extend its potential applicability beyond dental care. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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12 pages, 2091 KiB  
Article
Clinical Efficacy of Hyaluronic Acid with Iodine in Hard-to-Heal Wounds
by Jana Pecová, Vladimíra Rohlíková, Markéta Šmoldasová and Jan Marek
Pharmaceutics 2023, 15(9), 2268; https://doi.org/10.3390/pharmaceutics15092268 - 01 Sep 2023
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Abstract
Hard-to-heal wounds do not heal spontaneously and need long-term care provided by specialists. That burdens the patients as well as the healthcare systems. Such wounds arise from several pathologies, which result in venous leg ulcers (VLU), diabetic foot ulcers (DFU), pressure ulcers (PU), [...] Read more.
Hard-to-heal wounds do not heal spontaneously and need long-term care provided by specialists. That burdens the patients as well as the healthcare systems. Such wounds arise from several pathologies, which result in venous leg ulcers (VLU), diabetic foot ulcers (DFU), pressure ulcers (PU), or ulcers originating from post-surgical wounds (pSW). Given the complex nature of hard-to-heal wounds, novel treatments are sought to enable wound healing. We tested the clinical efficacy and applicability of fluid comprising hyaluronic acid and iodine complex (HA-I) in the treatment of hard-to-heal wounds. Patients (n = 56) with VLU, DFU, PU, or pSW hospitalised in multiple wound-care centres in the Czech Republic were treated with HA-I. Wound size, classically visible signs of infection, exudation, pain, and wound bed appearance were monitored for 12 weeks. The highest healing rate was in DFU (71.4%), followed by pSW (62.5%), VLU (55.6%), and PU (44.4%). Classical visible signs of infection were resolved within 8 weeks in all types of wounds. Wound bed appearance improved most noticeably in pSW and then in VLU. Exudation was lowered most significantly in DFU and pSW. The highest decrease in pain was in pSW and DFU. The treatment with HA-I successfully led to either complete closure or significant improvement in the wound’s healing. Therefore, the complex of hyaluronic acid and iodine is suitable for the treatment of hard-to-heal wounds of various aetiologies. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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18 pages, 4673 KiB  
Article
Injectable Hyaluronan-Based Thermoresponsive Hydrogels for Dermatological Applications
by Si Gou, Alexandre Porcello, Eric Allémann, Denis Salomon, Patrick Micheels, Olivier Jordan and Yogeshvar N. Kalia
Pharmaceutics 2023, 15(6), 1708; https://doi.org/10.3390/pharmaceutics15061708 - 11 Jun 2023
Cited by 4 | Viewed by 1442
Abstract
Most marketed HA-based dermal fillers use chemical cross-linking to improve mechanical properties and extend their lifetime in vivo; however, stiffer products with higher elasticity require an increased extrusion force for injection in clinical practice. To balance longevity and injectability, we propose a thermosensitive [...] Read more.
Most marketed HA-based dermal fillers use chemical cross-linking to improve mechanical properties and extend their lifetime in vivo; however, stiffer products with higher elasticity require an increased extrusion force for injection in clinical practice. To balance longevity and injectability, we propose a thermosensitive dermal filler, injectable as a low viscosity fluid that undergoes gelation in situ upon injection. To this end, HA was conjugated via a linker to poly(N-isopropylacrylamide) (pNIPAM), a thermosensitive polymer using “green chemistry”, with water as the solvent. HA-L-pNIPAM hydrogels showed a comparatively low viscosity (G′ was 105.1 and 233 for Candidate1 and Belotero Volume®, respectively) at room temperature and spontaneously formed a stiffer gel with submicron structure at body temperature. Hydrogel formulations exhibited superior resistance against enzymatic and oxidative degradation and could be administered using a comparatively lower injection force (49 N and >100 N for Candidate 1 and Belotero Volume®, respectively) with a 32G needle. Formulations were biocompatible (viability of L929 mouse fibroblasts was >100% and ~85% for HA-L-pNIPAM hydrogel aqueous extract and their degradation product, respectively), and offered an extended residence time (up to 72 h) at the injection site. This property could potentially be exploited to develop sustained release drug delivery systems for the management of dermatologic and systemic disorders. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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30 pages, 2981 KiB  
Article
Thermo-Responsive Hyaluronan-Based Hydrogels Combined with Allogeneic Cytotherapeutics for the Treatment of Osteoarthritis
by Alexandre Porcello, Paula Gonzalez-Fernandez, Annick Jeannerat, Cédric Peneveyre, Philippe Abdel-Sayed, Corinne Scaletta, Wassim Raffoul, Nathalie Hirt-Burri, Lee Ann Applegate, Eric Allémann, Alexis Laurent and Olivier Jordan
Pharmaceutics 2023, 15(5), 1528; https://doi.org/10.3390/pharmaceutics15051528 - 18 May 2023
Cited by 4 | Viewed by 1230
Abstract
Thermo-responsive hyaluronan-based hydrogels and FE002 human primary chondroprogenitor cell sources have both been previously proposed as modern therapeutic options for the management of osteoarthritis (OA). For the translational development of a potential orthopedic combination product based on both technologies, respective technical aspects required [...] Read more.
Thermo-responsive hyaluronan-based hydrogels and FE002 human primary chondroprogenitor cell sources have both been previously proposed as modern therapeutic options for the management of osteoarthritis (OA). For the translational development of a potential orthopedic combination product based on both technologies, respective technical aspects required further optimization phases (e.g., hydrogel synthesis upscaling and sterilization, FE002 cytotherapeutic material stabilization). The first aim of the present study was to perform multi-step in vitro characterization of several combination product formulas throughout the established and the optimized manufacturing workflows, with a strong focus set on critical functional parameters. The second aim of the present study was to assess the applicability and the efficacy of the considered combination product prototypes in a rodent model of knee OA. Specific characterization results (i.e., spectral analysis, rheology, tribology, injectability, degradation assays, in vitro biocompatibility) of hyaluronan-based hydrogels modified with sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(N-isopropylacrylamide) (HA-L-PNIPAM) containing lyophilized FE002 human chondroprogenitors confirmed the suitability of the considered combination product components. Specifically, significantly enhanced resistance toward oxidative and enzymatic degradation was shown in vitro for the studied injectable combination product prototypes. Furthermore, extensive multi-parametric (i.e., tomography, histology, scoring) in vivo investigation of the effects of FE002 cell-laden HA-L-PNIPAM hydrogels in a rodent model revealed no general or local iatrogenic adverse effects, whereas it did reveal some beneficial trends against the development of knee OA. Overall, the present study addressed key aspects of the preclinical development process for novel biologically-based orthopedic combination products and shall serve as a robust methodological basis for further translational investigation and clinical work. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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Review

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18 pages, 603 KiB  
Review
Hyaluronic Acid in Rheumatology
by Haiko Sprott and Christian Fleck
Pharmaceutics 2023, 15(9), 2247; https://doi.org/10.3390/pharmaceutics15092247 - 30 Aug 2023
Cited by 1 | Viewed by 1744
Abstract
Hyaluronic acid (HA), also known as hyaluronan, is an anionic glycosaminoglycan widely distributed throughout various tissues of the human body. It stands out from other glycosaminoglycans as it lacks sulfation and can attain considerable size: the average human synovial HA molecule weighs about [...] Read more.
Hyaluronic acid (HA), also known as hyaluronan, is an anionic glycosaminoglycan widely distributed throughout various tissues of the human body. It stands out from other glycosaminoglycans as it lacks sulfation and can attain considerable size: the average human synovial HA molecule weighs about 7 million Dalton (Da), equivalent to roughly 20,000 disaccharide monomers; although some sources report a lower range of 3–4 million Da. In recent years, HA has garnered significant attention in the field of rheumatology due to its involvement in joint lubrication, cartilage maintenance, and modulation of inflammatory and/or immune responses. This review aims to provide a comprehensive overview of HA’s involvement in rheumatology, covering its physiology, pharmacology, therapeutic applications, and potential future directions for enhancing patient outcomes. Nevertheless, the use of HA therapy in rheumatology remains controversial with conflicting evidence regarding its efficacy and safety. In conclusion, HA represents a promising therapeutic option to improve joint function and alleviate inflammation and pain. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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Other

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11 pages, 1228 KiB  
Systematic Review
The Effect of Adjunctive Use of Hyaluronic Acid on Prevalence of Porphyromonas gingivalis in Subgingival Biofilm in Patients with Chronic Periodontitis: A Systematic Review
by Fahad A. Alshehri and Meshal S. Alharbi
Pharmaceutics 2023, 15(7), 1883; https://doi.org/10.3390/pharmaceutics15071883 - 04 Jul 2023
Viewed by 838
Abstract
Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic bacterium that plays an important role in the development and progression of periodontitis. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has previously demonstrated antibacterial potential in vitro against multiple bacterial species, [...] Read more.
Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic bacterium that plays an important role in the development and progression of periodontitis. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has previously demonstrated antibacterial potential in vitro against multiple bacterial species, including P. gingivalis. The purpose of this systematic review is to evaluate the effectiveness of HA as an adjunctive topical antibacterial agent to non-surgical mechanical therapy of periodontitis in reducing the prevalence of P. gingivalis in subgingival biofilms. Five clinical studies were identified that satisfied the eligibility criteria. Only three trials were suitable for the meta-analysis as they provided data at three and six months. Data on the prevalence of P. gingivalis in each study were collected. The odds ratio (OR) for measuring the effect size with a 95% confidence interval (CI) was applied to the available data. The results did not favor the use of HA during non-surgical mechanical therapy to reduce the prevalence of P. gingivalis in subgingival biofilm (odd ratio = 0.95 and 1.11 at three and six months, consecutively). Within their limitations, the current data do not indicate an advantage for using HA during mechanical periodontal therapy to reduce the prevalence of P. gingivalis. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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